Digital Commons Network^™

Astct Consensus Grading For Cytokine Release Syndrome And Neurologic Toxicity Associated With Immune Effector Cells, Daniel W Lee, Armin Ghobadi, John F Dipersio, Et Al

Open Access Publications

Chimeric antigen receptor (CAR) T cell therapy is rapidly emerging as one of the most promising therapies for hematologic malignancies. Two CAR T products were recently approved in the United States and Europe for the treatment ofpatients up to age 25years with relapsed or refractory B cell acute lymphoblastic leukemia and/or adults with large B cell lymphoma. Many more CAR T products, as well as other immunotherapies, including various immune cell- and bi-specific antibody-based approaches that function by activation of immune effector cells, are in clinical development for both hematologic and solid tumor malignancies. These therapies are associated with unique …

Matching Mitochondrial Dna Haplotypes For Circumventing Tissue-Specific Segregation Bias, Jianxin Pan, Li Wang, Charles Lu, Yanming Zhu, Zhunyuan Min, Xi Dong, Hongying Sha

Open Access Publications

Mitochondrial DNA (mtDNA) segregation associated with donor-recipient mtDNA mismatch in mitochondria replacement therapy leads to unknown risks. Here, to explore whether matching mtDNA haplotypes contributes to ameliorating segregation, we reproduced various degrees of heteroplasmic mice with three single nucleotide polymorphisms to monitor segregation severity. "Segregation" presented in tissues of heteroplasmic mice containing low-level donor mtDNA heteroplasmy, and disappeared as donor mtDNA heteroplasmy levels ascended. Meanwhile, we found that distribution of donor mtDNA among the blastomeres of preimplantation embryos from the heteroplasmic mice shared the same tendency as that in adult tissues. Statistical analysis showed that no selective replication of donor …

Neurotransmitter Identity Is Acquired In A Lineage-Restricted Manner In The Drosophila Cns, Haluk Lacin, Hui-Min Chen, Xi Long, Robert H. Singer, Tzumin Lee, James W. Truman

Open Access Publications

The vast majority of the adult fly ventral nerve cord is composed of 34 hemilineages, which are clusters of lineally related neurons. Neurons in these hemilineages use one of the three fast-acting neurotransmitters (acetylcholine, GABA, or glutamate) for communication. We generated a comprehensive neurotransmitter usage map for the entire ventral nerve cord. We did not find any cases of neurons using more than one neurotransmitter, but found that the acetylcholine specific gene ChAT is transcribed in many glutamatergic and GABAergic neurons, but these transcripts typically do not leave the nucleus and are not translated. Importantly, our work uncovered a simple …

Skin Cancer Precursor Immunotherapy For Squamous Cell Carcinoma Prevention, Abby R Rosenberg, Mary Tabacchi, Kenneth H Ngo, Michael Wallendorf, Ilana S Rosman, Lynn A Cornelius, Shadmehr Demehri

Open Access Publications

BACKGROUND: Topical calcipotriol plus 5-fluorouracil (5-FU) combination is an effective immunotherapy against actinic keratosis (AK), which is a precursor to squamous cell carcinoma (SCC). However, the long-term effectiveness of calcipotriol plus 5-FU treatment for SCC prevention is unknown.

METHODS: We performed a blinded prospective cohort study on participants of a randomized double-blind clinical trial in which a 4-day course of topical calcipotriol plus 5-FU combination was compared to Vaseline plus 5-FU (control) for AK treatment. SCC and basal cell carcinoma (BCC) incidences were assessed at 1, 2, and 3 years after trial. Tissues were analyzed for calcipotriol plus 5-FU-induced T …

A Novel Pathogenic Variant In Osbpl2 Linked To Hereditary Late-Onset Deafness In A Mongolian Family, Ningjin Wu, Husile Husile, Liqing Yang, Yaning Cao, Xing Li, Wenyan Huo, Haihua Bai, Yangjian Liu, Qizhu Wu

Open Access Publications

BACKGROUND: To investigate the clinical features and the underlying causal gene of a family with hereditary late-onset deafness in Inner Mongolia of China, and to provide evidence for the early genetic screening and diagnosis of this disease.

METHODS: Family data were collected to draw a pedigree. Audiological testing and physical examination of the family members were conducted following questionnaire. Genomic DNA was extracted from peripheral blood of 5 family members (3 patients and 2 normal control) and subjected to whole genome sequencing for identifying deafness casual genes. The pathogenic variant in the deafness gene was further confirmed by Sanger sequencing. …

Network Meta-Analysis Of Randomised Trials Of Pharmacological, Psychotherapeutic, Exercise And Collaborative Care Interventions For Depressive Symptoms In Patients With Coronary Artery Disease: Hybrid Systematic Review Of Systematic Reviews Protocol, Frank Doyle, Kenneth Freedland, Robert Carney, Peter De Jonge, Chris Dickens, Susanne Pedersen, Jan Sorensen, Martin Dempster

Open Access Publications

BACKGROUND: Depression is common in patients with coronary artery disease (CAD) and is associated with poorer outcomes and higher costs. Several randomised controlled trials (RCTs) targeting depression, of various modalities (including pharmacological, psychotherapeutic and other approaches), have been conducted and summarised in pairwise meta-analytic reviews. However, no study has considered the cumulative evidence within a network, which can provide valuable indirect comparisons and information about the relative efficacy of interventions. Therefore, we will adopt a review of review methodology to develop a network meta-analysis (NMA) of depression interventions for depression in CAD.

METHODS: We will search relevant databases from inception …

Homozygous Frameshift Mutations In Fat1 Cause A Syndrome Characterized By Colobomatous-Microphthalmia, Ptosis, Nephropathy And Syndactyly., Najim Lahrouchi, Aman George, Ilham Ratbi, Ronen Schneider, Siham C Elalaoui, Shahida Moosa, Sanita Bharti, Ruchi Sharma, Mones Abu-Asab, Felix Onojafe, Najlae Adadi, Elisabeth M Lodder, Fatima-Zahra Laarabi, Yassine Lamsyah, Hamza Elorch, Imane Chebbar, Alex V Postma, Vassilios Lougaris, Alessandro Plebani, Janine Altmueller, Henriette Kyrieleis, Vardiella Meiner, Helen Mcneill, Kapil Bharti, Stanislas Lyonnet, Bernd Wollnik, Alexandra Henrion-Caude, Amina Berraho, Friedhelm Hildebrandt, Connie R Bezzina, Brian P Brooks, Abdelaziz Sefiani

Open Access Publications

A failure in optic fissure fusion during development can lead to blinding malformations of the eye. Here, we report a syndrome characterized by facial dysmorphism, colobomatous microphthalmia, ptosis and syndactyly with or without nephropathy, associated with homozygous frameshift mutations in FAT1. We show that Fat1 knockout mice and zebrafish embryos homozygous for truncating fat1a mutations exhibit completely penetrant coloboma, recapitulating the most consistent developmental defect observed in affected individuals. In human retinal pigment epithelium (RPE) cells, the primary site for the fusion of optic fissure margins, FAT1 is localized at earliest cell-cell junctions, consistent with a role in facilitating optic …

Follicular Lymphoma Patients With Kir2dl2 And Kir3dl1 And Their Ligands (Hla-C1 And Hla-Bw4) Show Improved Outcome When Receiving Rituximab, Amy K Erbe, Wei Wang, Lakeesha Carmichael, Anna Hoefges, Bartosz Grzywacz, Patrick K Reville, Erik A Ranheim, Jacquelyn A Hank, Kyungmann Kim, Songwon Seo, Eneida A Mendonca, Yiqiang Song, Vaishalee P Kenkre, Fangxin Hong, Randy D Gascoyne, Elisabeth Paietta, Sandra J Horning, Jeffrey S Miller, Brad Kahl, Paul M Sondel

Open Access Publications

BACKGROUND: The ECOG-ACRIN Cancer Research Group evaluated rituximab treatment schedules for patients with newly-diagnosed low-tumor-burden follicular-lymphoma (FL). All patients received 4-weekly rituximab treatments as induction therapy. Clinically-responding patients were randomized to receive rituximab every 13 weeks ("maintenance") vs. no additional rituximab until progression ("non-maintenance"). Based on "time-to-rituximab-failure (TTRF)", the study-committee reported there was no overall-benefit for maintenance rituximab in this setting. Tumor-reactive mAbs, like rituximab, trigger natural killer (NK) cells. NK-cell responses are regulated, in part, by interactions between killer immunoglobulin-like receptors (KIRs) on NK cells and their interactions with KIR-ligands. In a separate study of children with neuroblastoma treated …

Temperoammonic Stimulation Depotentiates Schaffer Collateral Ltp Via P38 Mapk Downstream Of Adenosine A1 Receptors, Yukitoshi Izumi, Charles F. Zorumski

Open Access Publications

We previously found that low-frequency stimulation of direct temperoammonic (TA) inputs to hippocampal area CA1 depotentiates previously established long-term potentiation in the Schaffer collateral (SC) pathway through complex signaling involving dopamine, endocannabinoids, neuregulin-1, GABA, and adenosine, with adenosine being the most distal modulator identified to date. In the present studies, we examined mechanisms contributing to the effects of adenosine in hippocampal slices from male albino rats. We found that extracellular conversion of ATP to adenosine via an ectonucleotidase contributes significantly to TA-mediated SC depotentiation and the depotentiation resulting from block of adenosine transport. Adenosine-mediated SC depotentiation does not involve activation …

Covert Pathogenesis: Transient Exposures To Microbes As Triggers Of Disease, Nicole M. Gilbert, Amanda L. Lewis

Open Access Publications

No abstract provided.

Staying Awake To Stay Alive: A Circuit Controlling Starvation-Induced Waking, Krishna Melnattur, Paul Shaw

Open Access Publications

The balance of sleep and wake is plastic and changes to meet environmental demands. Mechanisms that allow an animal to suppress sleep and maintain waking in potentially adverse situations could serve adaptive functions in evolution. The fruit fly, Drosophila melanogaster, is well poised as a system in which to explore these questions. The environment changes sleep and wake in flies, e.g., starvation induces waking in Drosophila as it does in many animals. Further, the sophisticated neurobiological toolkit available to Drosophila researchers gives the fly a great advantage as a system to investigate the precise neurobiological mechanisms underlying these adaptive changes. …

Genetics Of Group A Streptococci, Kyu Hong Cho, Gary C Port, Michael Caparon

Open Access Publications

No abstract provided.

Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, And Exploratory Efficacy Of The Novel Enzyme Replacement Therapy Avalglucosidase Alfa (Neogaa) In Treatment-Naïve And Alglucosidase Alfa-Treated Patients With Late-Onset Pompe Disease: A Phase 1, Open-Label, Multicenter, Multinational, Ascending Dose Study, Loren D M Pena, Alan Pestronk, Et Al

Open Access Publications

This multicenter/multinational, open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat-dose avalglucosidase alfa (neoGAA), a second-generation, recombinant acid α-glucosidase replacement therapy, in late-onset Pompe disease (LOPD). Patients ≥18 years, alglucosidase alfa naïve (Naïve) or previously receiving alglucosidase alfa for ≥9 months (Switch), with baseline FVC ≥50% predicted and independently ambulatory, received every-other-week avalglucosidase alfa 5, 10, or 20 mg/kg over 24 weeks. 9/10 Naïve and 12/14 Switch patients completed the study. Avalglucosidase alfa was well-tolerated; no deaths/life-threatening serious adverse events (SAEs). One Naïve patient withdrew for study drug-related SAEs (respiratory distress/chest discomfort). Infusion-associated reactions (IARs) …

Association Of The Infant Gut Microbiome With Early Childhood Neurodevelopmental Outcomes: An Ancillary Study To The Vdaart Randomized Clinical Trial, Joanne E. Sordillo, Susan Korrick, Nancy Laranjo, Vincent Carey, George M. Weinstock, Diane R. Gold, George O'Connor, Megan Sandel, Leonard B. Bacharier, Avraham Beigelman, Robert Zeiger, Augusto A. Litonjua, Scott T. Weiss

Open Access Publications

Importance: In animal models, the early life gut microbiome influences later neurodevelopment. Corresponding data in human populations are lacking.

Objective: To study associations between the gut microbiome in infants and development at preschool age measured by the Ages and Stages Questionnaire, third edition (ASQ-3).

Design, Setting, and Participants: This ancillary cohort study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART) used data from 715 participants who had development assessed at 3 years of age by the ASQ-3, which included scores in 5 domains (gross motor skills, fine motor skills, problem solving, communication, and personal and social skills). A total …

Comparison Of A Prototype For Indications-Based Prescribing With 2 Commercial Prescribing Systems, Pamela M. Garabedian, Joanna Abraham, Et Al

Open Access Publications

Importance: The indication (reason for use) for a medication is rarely included on prescriptions despite repeated recommendations to do so. One barrier has been the way existing electronic prescribing systems have been designed.

Objective: To evaluate, in comparison with the prescribing modules of 2 leading electronic health record prescribing systems, the efficiency, error rate, and satisfaction with a new computerized provider order entry prototype for the outpatient setting that allows clinicians to initiate prescribing using the indication.

Design, Setting, and Participants: This quality improvement study used usability tests requiring internal medicine physicians, residents, and physician assistants to enter prescriptions electronically, …

Association Of Blood Concentrations Of Complement Split Product Ic3b And Serum C3 With Systemic Lupus Erythematosus Disease Activity, Alfred H J Kim, Vibeke Strand, Deepali P Sen, Qiang Fu, Nancy L Mathis, Martin J Schmidt, Robin R Bruchas, Nick R Staten, Paul K Olson, Chad M Stiening, John P Atkinson

Open Access Publications

OBJECTIVE: To examine correlations between blood levels of complement split product iC3b and serum component C3 with clinically meaningful changes in disease activity in patients with systemic lupus erythematosus (SLE).

METHODS: A total of 159 consecutive patients with SLE, diagnosed according to the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria, were enrolled in CASTLE (Complement Activation Signatures in Systemic Lupus Erythematosus), a prospective observational study. Patients with 1-7 study visits were included in this longitudinal analysis. In addition, 48 healthy volunteers were enrolled to establish a normal reference value for the ratio of blood iC3b …

Levels And Patterns Of Self-Reported And Objectively-Measured Free-Living Physical Activity Among Prostate Cancer Survivors: A Prospective Cohort Study, Lee Smith, Jung Ae Lee, Junbae Mun, Ratna Pakpahan, Kellie R Imm, Sonya Izadi, Adam S Kibel, Graham A Colditz, Robert L Grubb Iii, Kathleen Y Wolin, Siobhan Sutcliffe, Lin Yang

Open Access Publications

BACKGROUND: No prior study has measured or compared self-reported and objectively measured physical activity trajectories in prostate cancer survivors before and after treatment.

METHODS: Clinically localized prostate cancer patients treated with radical prostatectomy were recruited between 2011 and 2014. Of the 350 participants enrolled at the main site, 310 provided self-reported physical activity at baseline before radical prostatectomy, and 5 weeks, 6 months, and 12 months after radical prostatectomy. A subset of participants (n = 81) provided objectively measured physical activity at all study time points by wearing an accelerometer for 7 days each. Changes in activity over time were …

Insulin Resistance And Chronic Kidney Disease Progression, Cardiovascular Events, And Death: Findings From The Chronic Renal Insufficiency Cohort Study, Sarah J Schrauben, Patricia Kao, Et Al

Open Access Publications

BACKGROUND: Insulin resistance contributes to the metabolic syndrome, which is associated with the development of kidney disease. However, it is unclear if insulin resistance independently contributes to an increased risk of chronic kidney disease (CKD) progression or CKD complications. Additionally, predisposing factors responsible for insulin resistance in the absence of diabetes in CKD are not well described. This study aimed to describe factors associated with insulin resistance and characterize the relationship of insulin resistance to CKD progression, cardiovascular events and death among a cohort of non-diabetics with CKD.

METHODS: Data was utilized from Chronic Renal Insufficiency Cohort Study participants without …

Plaidoh: A Novel Method For Functional Prediction Of Long Non-Coding Rnas Identifies Cancer-Specific Lncrna Activities, Sarah C Pyfrom, Hong Luo, Jacqueline E Payton

Open Access Publications

BACKGROUND: Long non-coding RNAs (lncRNAs) exhibit remarkable cell-type specificity and disease association. LncRNA's functional versatility includes epigenetic modification, nuclear domain organization, transcriptional control, regulation of RNA splicing and translation, and modulation of protein activity. However, most lncRNAs remain uncharacterized due to a shortage of predictive tools available to guide functional experiments.

RESULTS: To address this gap for lymphoma-associated lncRNAs identified in our studies, we developed a new computational method, Predicting LncRNA Activity through Integrative Data-driven 'Omics and Heuristics (PLAIDOH), which has several unique features not found in other methods. PLAIDOH integrates transcriptome, subcellular localization, enhancer landscape, genome architecture, chromatin interaction, …

Comprehensive Gene Expression Meta-Analysis Identifies Signature Genes That Distinguish Microglia From Peripheral Monocytes/Macrophages In Health And Glioma, Verena Haage, Marcus Semtner, Ramon Oliveira Vidal, Daniel Perez Hernandez, Winnie W Pong, Zhihong Chen, Dolores Hambardzumyan, Vincent Magrini, Amy Ly, Jason Walker, Elaine Mardis, Philipp Mertins, Sascha Sauer, Helmut Kettenmann, David H Gutmann

Open Access Publications

Monocytes/macrophages have begun to emerge as key cellular modulators of brain homeostasis and central nervous system (CNS) disease. In the healthy brain, resident microglia are the predominant macrophage cell population; however, under conditions of blood-brain barrier leakage, peripheral monocytes/macrophages can infiltrate the brain and participate in CNS disease pathogenesis. Distinguishing these two populations is often challenging, owing to a paucity of universally accepted and reliable markers. To identify discriminatory marker sets for microglia and peripheral monocytes/macrophages, we employed a large meta-analytic approach using five published murine transcriptional datasets. Following hierarchical clustering, we filtered the top differentially expressed genes (DEGs) through …

Ilc2s Are The Predominant Source Of Intestinal Ilc-Derived Il-10, Jennifer K Bando, Susan Gilfillan, Blanda Di Luccia, José L Fachi, Cristiane Sécca, Marina Cella, Marco Colonna

Open Access Publications

Although innate lymphoid cells (ILCs) functionally analogous to T helper type 1 (Th1), Th2, and Th17 cells are well characterized, an ILC subset strictly equivalent to IL-10-secreting regulatory T cells has only recently been proposed. Here, we report the absence of an intestinal regulatory ILC population distinct from group 1 ILCs (ILC1s), ILC2s, and ILC3s in (1) mice bred in our animal facility; (2) mice from The Jackson Laboratory, Taconic Biosciences, and Charles River Laboratories; and (3) mice subjected to intestinal inflammation. Instead, a low percentage of intestinal ILC2s produced IL-10 at steady state. A screen for putative IL-10 elicitors …

Gene Therapy Targeting Sarm1 Blocks Pathological Axon Degeneration In Mice, Stefanie Geisler, Shay X. Huang, Amy Strickland, Ryan A. Doan, Daniel W. Summers, Xianrong Mao, Jiwoong Park, Aaron Diantonio, Jeffrey Milbrandt

Open Access Publications

Axonal degeneration (AxD) following nerve injury, chemotherapy, and in several neurological disorders is an active process driven by SARM1, an injury-activated NADase. Axons of SARM1-null mice exhibit greatly delayed AxD after transection and in models of neurological disease, suggesting that inhibiting SARM1 is a promising strategy to reduce pathological AxD. Unfortunately, no drugs exist to target SARM1. We, therefore, developed SARM1 dominant-negatives that potently block AxD in cellular models of axotomy and neuropathy. To assess efficacy in vivo, we used adeno-associated virus-mediated expression of the most potent SARM1 dominant-negative and nerve transection as a model of severe AxD. While axons …

Outcomes And Toxicity Following Yttrium-90 Radioembolization For Hepatic Metastases From Neuroendocrine Tumors-A Single-Institution Experience, Darryl A. Zuckerman, Richard F. Kennard, Amit Roy, Parag J. Parikh, Ashley A. Weiner

Open Access Publications

Background: The prognosis of patients with hepatic metastases from neuroendocrine tumors (NET) is generally good, and radioembolization with Yttrium-90 microspheres is a locoregional therapy that is used in efforts to improve hepatic disease control and survival. This study aims to describe the survival outcomes and toxicities associated with radioembolization for hepatic-predominant metastatic NET in a large single-institution cohort.

Methods: A total of 59 patients underwent radioembolization for metastatic NET with hepatic predominant disease at a single academic center. Patient outcomes were analyzed by Kaplan-Meier survival analysis and toxicities were detailed and described. Ten patients within the cohort underwent post-treatment dosimetric …

Napoli-1 Phase 3 Study Of Liposomal Irinotecan In Metastatic Pancreatic Cancer: Final Overall Survival Analysis And Characteristics Of Long-Term Survivors, Andrea Wang-Gillam, Richard A Hubner, Jens T Siveke, Daniel D Von Hoff, Bruce Belanger, Floris A De Jong, Beloo Mirakhur, Li-Tzong Chen

Open Access Publications

BACKGROUND: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is approved for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This approval was based on significantly improved median overall survival compared with 5-FU/LV alone (6.1 vs 4.2 months; hazard ratio [HR], 0.67) in the global phase 3 NAPOLI-1 trial. Here, we report the final survival analysis and baseline characteristics associated with long-term survivors (survival of ≥1 year) in the NAPOLI-1 trial.

PATIENTS AND METHODS: Patients with mPDAC were randomised to receive nal-IRI + 5-FU/LV (n = 117), nal-IRI (n = 151), or 5-FU/LV (n = 149) …

Empiric Radiotherapy For Lung Cancer Collaborative Group Multi-Institutional Evidence-Based Guidelines For The Use Of Empiric Stereotactic Body Radiation Therapy For Non-Small Cell Lung Cancer Without Pathologic Confirmation, Abigail T Berman, Salma K Jabbour, Anil Vachani, Cliff Robinson, J. Isabelle Choi, Pranshu Mohindra, Ramesh Rengan, Jeffrey Bradley, Charles B Simone Ii

Open Access Publications

The standard of care for managing early stage non-small cell lung cancer (NSCLC) is definitive surgical resection. Stereotactic body radiation therapy (SBRT) has become the standard treatment for patient who are medically inoperable, and it is increasingly being considered as an option in operable patients. With the growing use of screening thoracic CT scans for patients with a history of heavy smoking, as well as improved imaging capabilities, the discovery of small lung nodes has become a common dilemma. As a result, clinicians are increasingly faced with managing lung nodules in patients in whom diagnostic biopsy is not safe or …

Combining Stereotactic Body Radiation Therapy With Immunotherapy: Current Data And Future Directions, Alexander J Lin, Michael Roach, Jeffrey Bradley, Clifford Robinson

Open Access Publications

Stereotactic body radiation therapy (SBRT) offers excellent local control of early-stage non-small cell lung cancer (NSCLC), but there currently is a need for tolerable systemic therapy to address regional and distant disease progression. One potential option is immunotherapy, which in metastatic NSCLC has shown promise for sustained disease control in a subset of patients. There is also growing evidence for a clinical synergy between radiation and immunotherapy, with several ongoing trials studying the abscopal effect. This review summarizes the current data in the fast-changing field of immuno-radiation therapy, highlighting updates from recent clinical trials.

Prevalence, Underlying Causes, And Preventability Of Sepsis-Associated Mortality In Us Acute Care Hospitals, Chanu Rhee, Travis M. Jones, Yasir Hamad, Anupam Pande, Jack Varon, Cara O'Brien, Deverick J Anderson, David K. Warren, Raymund B. Dantes, Lauren Epstein, Michael Klompas

Open Access Publications

Importance: Sepsis is present in many hospitalizations that culminate in death. The contribution of sepsis to these deaths, and the extent to which they are preventable, is unknown.

Objective: To estimate the prevalence, underlying causes, and preventability of sepsis-associated mortality in acute care hospitals.

Design, Setting, and Participants: Cohort study in which a retrospective medical record review was conducted of 568 randomly selected adults admitted to 6 US academic and community hospitals from January 1, 2014, to December 31, 2015, who died in the hospital or were discharged to hospice and not readmitted. Medical records were reviewed from January 1, …

Lats1/2 Kinases Trigger Self-Renewal Of Cancer Stem Cells In Aggressive Oral Cancer, Masami Nozaki, Norikazu Yabuta, Moe Fukuzawa, Satomi Mukai, Ayumi Okamoto, Towa Sasakura, Kohshiro Fukushima, Yoko Naito, Gregory D. Longmore, Hiroshi Nojima

Open Access Publications

Cancer stem cells (CSCs), which play important roles in tumor initiation and progression, are resistant to many types of therapies. However, the regulatory mechanisms underlying CSC-specific properties, including self-renewal, are poorly understood. Here, we found that LATS1/2, the core Hippo pathway-kinases, were highly expressed in the oral squamous cell carcinoma line SAS, which exhibits high capacity of CSCs, and that depletion of these kinases prevented SAS cells from forming spheres under serum-free conditions. Detailed examination of the expression and activation of LATS kinases and related proteins over a time course of sphere formation revealed that LATS1/2 were more highly expressed …

Comprehensive Behavioral And Biochemical Outcomes Of Novel Murine Models Of Gm1-Gangliosidosis And Morquio Syndrome Type B, Michael J Przybilla, Li Ou, Alexandru-Flaviu Tăbăran, Xuntian Jiang, Rohini Sidhu, Pamela J Kell, Daniel S Ory, M Gerard O'Sullivan, Chester B Whitley

Open Access Publications

Deficiencies in the lysosomal hydrolase β-galactosidase (β-gal) lead to two distinct diseases: the skeletal disease Morquio syndrome type B, and the neurodegenerative disease GM1-gangliosidosis. Utilizing CRISPR-Cas9 genome editing, the mouse β-gal encoding gene, Glb1, was targeted to generate both models of β-gal deficiency in a single experiment. For Morquio syndrome type B, the common human missense mutation W273L (position 274 in mice) was introduced into the Glb1 gene (Glb1

An Observational Study Of End-Tidal Carbon Dioxide Trends In General Anesthesia, Annemarie Akkermans, Judith A R Van Waes, Aleda Thompson, Amy Shanks, Linda M Peelen, Michael F Aziz, Daniel A Biggs, William C Paganelli, Jonathan P Wanderer, Daniel L Helsten, Sachin Kheterpal, Wilton A Van Klei, Leif Saager

Open Access Publications

PURPOSE: Despite growing evidence supporting the potential benefits of higher end-tidal carbon dioxide (ETCO

METHODS: This retrospective, observational, multicentre study included 317,445 adult patients who received general anesthesia for non-cardiothoracic procedures between January 2008 and September 2016. The primary outcome was a time-weighted average area-under-the-curve (TWA-AUC) for four ETCO

RESULTS: Both TWA-AUC and median ETCO

CONCLUSIONS: Between 2008 and 2016, intraoperative ETCO